Single-cell sequencing reveals αβ chain pairing shapes the T cell repertoire

Grigaityte, K.; Carter, J. A.; Goldfless, S. J.; Jeffery, E. W.; Hause, R. J.; Jiang, Y.; Koppstein, D.; Briggs, A. W.; Church, G. M.; Vigneault, F.; Atwal, G. S.

doi:10.1101/213462

bioRxiv · 10.1101/213462

Single-cell sequencing reveals αβ chain pairing shapes the T cell repertoire

Grigaityte, K.·Carter, J. A.·Goldfless, S. J.·Jeffery, E. W.·Hause, R. J.·Jiang, Y.·Koppstein, D.·Briggs, A. W.·Church, G. M.·Vigneault, F.·Atwal, G. S.

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Abstract

A diverse T cell repertoire is a critical component of the adaptive immune system, providing protection against invading pathogens and neoplastic changes, relying on the recognition of foreign antigens and neoantigen peptides by T cell receptors (TCRs). However, the statistical properties and function of the T cell pool in an individual, under normal physiological conditions, are poorly understood. In this study, we report a comprehensive, quantitative characterization of the T cell repertoire from over 1.9 million cells, yielding over 200,000 high quality paired {beta} sequences in 5 healthy human subjects. The dataset was obtained by leveraging recent biotechnology developments in deep RNA sequencing of lymphocytes via single-cell barcoding in emulsion. We report non-random associations and non-monogamous pairing between the and {beta} chains, lowering the theoretical diversity of the T cell repertoire, and increasing the frequency of public clones shared among individuals. T cell clone size distributions closely followed a power law, with markedly longer tails for CD8+ cytotoxic T cells than CD4+ helper T cells. Furthermore, clonality estimates based on paired chains from single T cells were lower than that from single chain data. Taken together, these results highlight the importance of sequencing {beta} pairs to accurately quantify lymphocyte receptor diversity.

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Grigaityte, K., Carter, J. A., Goldfless, S. J., Jeffery, E. W., Hause, R. J., Jiang, Y., Koppstein, D., Briggs, A. W., Church, G. M., Vigneault, F., Atwal, G. S.. 2017-11-02. Single-cell sequencing reveals αβ chain pairing shapes the T cell repertoire. https://doi.org/10.1101/213462

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